Pregnancy in humans and animals results in a number of adaptive metabolic responses in the mother in order to meet the energy and nutrient requirements of both the mother and the fetus in addition to providing substrates for fetal growth. Studies of alterations in glucose metabolism in pregnancy are underscored by the fact that glucose is: the major fuel for fetal oxidative metabolism, and perturbations in maternal glucose homeostasis in diabetes mellitus contributes to significant alterations in fetal growth and neonatal metabolism. The long range objective of the proposed studies is to examine the normal adaptive responses in glucose metabolism in pregnancy and study the effect of diabetes in pregnancy upon these adaptive responses. By combining the recently developed methods of Stable isotopic tracers, mass-spectrometry, respiratory calorimetry and glucose-clamp technique, the proposed studies will document the effects of insulin resistance of pregnancy on partitioning of glucose utilization by the mother, the effect of gestational diabetes on these processes and the reversibility of the altered metabolism in diabetes by treatment regimens. The other aims are to examine the circadian changes in glucose homeostasis and the effects of labor on maternal circulating substrates and related hormones. Although clinical protocols for the managements of normal and diabetic pregnancies have been defined, the scientific basis for these practices are not well established. The proposed studies are significant in that by using sophisticated scientific methods, they will document the glucose homeostasis in the normal pregnancy and thus provide s rationale for the clinical intervention in the abnormal states. The data from these studies will have immediate relevance to clinical care of human pregnancy.